The olfactory system provides a unique window into how genetically defined neuronal circuits give rise to normal brain function. Volatile odorants are detected by a large family of olfactory receptor genes, each of which is represented by a specific functional input to the brain. Progress towards understanding mammalian olfaction has been hindered by difficulties in identifying main olfactory receptor genes that contribute significantly to odor perception. This proposal addresses how individual members of a small main olfactory receptor family, the Trace Amine-Associated Receptors (TAARs), contribute to odor perception in mammals. The TAARs are conserved in humans, mice and other vertebrates suggesting an important function. We propose a combination of genetics, physiology and behavior to test the hypothesis that the TAARs are the most sensitive receptors in a distinct pathway that mediates innate aversion to amines-a biologically relevant class of odorants that are produced by decay and microbial action. Specific Aim 1 is to determine whether the TAARs contribute significantly to setting behavioral detection thresholds to amines. Specific Aim 2 is to determine whether selective activation of TAAR inputs can drive aversive behaviors. Specific Aim 3 is to determine whether remapping the location of TAAR inputs to the olfactory bulb alters odor perception. Achieving these aims will advance our understanding of how this novel chemosensory gene family contributes to olfaction, and how the organization of mammalian olfactory circuits influences odor perception in mammals, including humans.